title: IκBα polymorphisms were associated with increased risk of gastric cancer in a southern Chinese population: a case-control study.
abstract: OBJECTIVE
  Nuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case-control study among southern Chinese.
  
  
  METHODS
  A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2kb promoter region to the 3.5kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay.
  
  
  RESULTS
  rs17103265 deletion homozygote (-/-) had significantly increased gastric cancer risk (OR=2.11, 95% CI=1.17-3.83, P=0.01), compared with rs17103265 T homozygote (TT). rs17103265 (-/-) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR=2.21, 95% CI=1.19-4.08, P=0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (-/-) was associated with poorly differentiated gastric cancer (OR=2.05, 95% CI=1.07-3.94, P=0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P<0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients.
  
  
  CONCLUSIONS
  IκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population.
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Shiyan
authors.initials: S
authors.lastname: Wang
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zeng
authors.forename: Linwei
authors.initials: L
authors.lastname: Tian
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chu
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.forename: Pinjin
authors.initials: P
authors.lastname: Hu
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002681:China; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha